The proposed research program is directed to quantitatively characterize the lateral organization of molecules in biological membranes so that precise correlations can be established between membrane organization and membrane function. These studies will provide information concerning the disposition of molecules within lipid bilayer membranes in terms of the formation of clusters or domains of specific composition. These compositional domains will be characterized, using statistical thermodynamic methods, in terms of their size, number, geometry and topological localization within the membrane. The dependence of these molecular distributions on the composition, physical state of the bilayer and external physicochemical parameters like temperature, ionic strength, pH and the chemical composition of the medium will be assessed. These distributions will be obtained from the analysis of excess heat capacity functions and excess volume functions experimentally determined by scanning calorimetry and density measurements. The experimental studies will be performed in reconstituted membranes containing phosphatidylcholines, phosphatidylserines and glycosphingolipids (gangliosides and cerebrosides). The results of this research project will contribute to our understanding of the relationships between molecular organization and functional properties in biological membranes.